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Tracleer (Bosentan) - Summary



Because of the risks of hepatotoxicity and birth defects, Tracleer is available only through a restricted program called the Tracleer Access Program (T.A.P.). T.A.P. is a component of the Tracleer Risk Evaluation and Mitigation Strategy (REMS). Under the Tracleer REMS, prescribers, patients, and pharmacies must enroll in the program. [see Warnings and Precautions].


In clinical studies, Tracleer caused at least 3-fold upper limit of normal (ULN) elevation of liver aminotransferases (ALT and AST) in about 11% of patients, accompanied by elevated bilirubin in a small number of cases. Because these changes are a marker for potential serious hepatotoxicity, serum aminotransferase levels must be measured prior to initiation of treatment and then monthly [see Dosage and Administration, Warnings and Precautions]. In the postmarketing period, in the setting of close monitoring, rare cases of unexplained hepatic cirrhosis were reported after prolonged (> 12 months) therapy with Tracleer in patients with multiple comorbidities and drug therapies. There have also been reports of liver failure. The contribution of Tracleer in these cases could not be excluded.

In at least one case, the initial presentation (after > 20 months of treatment) included pronounced elevations in aminotransferases and bilirubin levels accompanied by non-specific symptoms, all of which resolved slowly over time after discontinuation of Tracleer. This case reinforces the importance of strict adherence to the monthly monitoring schedule for the duration of treatment and the treatment algorithm, which includes stopping Tracleer with a rise of aminotransferases accompanied by signs or symptoms of liver dysfunction [see Dosage and Administration].

Elevations in aminotransferases require close attention [see Dosage and Administration]. Tracleer should generally be avoided in patients with elevated aminotransferases (> 3 × ULN) at baseline because monitoring for hepatotoxicity may be more difficult. If liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin ≥ 2 × ULN, treatment with Tracleer should be stopped. There is no experience with the reintroduction of Tracleer in these circumstances.


Tracleer is likely to cause major birth defects if used by pregnant females based on animal data [see Use in Specific Populations]. Therefore, pregnancy must be excluded before the start of treatment with Tracleer. Throughout treatment and for one month after stopping Tracleer, females of childbearing potential must use two reliable methods of contraception unless the patient has a tubal sterilization or Copper T 380A IUD or LNg 20 IUS inserted, in which case no other contraception is needed. Hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives should not be used as the sole means of contraception because these may not be effective in patients receiving Tracleer [see Drug Interactions]. Obtain monthly pregnancy tests.



Tracleer is the proprietary name for bosentan, an endothelin receptor antagonist that belongs to a class of highly substituted pyrimidine derivatives, with no chiral centers.

Pulmonary Arterial Hypertension

Tracleer® is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%) [see Clinical Studies].

Considerations for use

Patients with WHO Class II symptoms showed reduction in the rate of clinical deterioration and a trend for improvement in walk distance. Physicians should consider whether these benefits are sufficient to offset the risk of hepatotoxicity in WHO Class II patients, which may preclude future use as their disease progresses.

See all Tracleer indications & dosage >>


Media Articles Related to Tracleer (Bosentan)

Medical News Today: Scientists discover new cell type behind pulmonary hypertension
Source: Featured Health News from Medical News Today [2015.10.08]
By studying human lung samples and a mouse model, scientists have discovered a new type of cell - and the molecular signals that regulate it - behind pulmonary hypertension.

Scientists discover new cell type behind pulmonary hypertension
Source: Biology / Biochemistry News From Medical News Today [2015.10.08]
By studying human lung samples and a mouse model, scientists have discovered a new type of cell - and the molecular signals that regulate it - behind pulmonary hypertension.

Pulmonary Hypertension
Source: MedicineNet sildenafil Specialty [2015.02.19]
Title: Pulmonary Hypertension
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 2/19/2015 12:00:00 AM

more news >>

Published Studies Related to Tracleer (Bosentan)

Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia. [2014]
receptor antagonist bosentan in this patient group... CONCLUSIONS: This study shows no difference in invasive pulmonary hemodynamics,

BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. [2011.07.01]
RATIONALE: A previous trial of bosentan in idiopathic pulmonary fibrosis (IPF) showed a trend to delayed IPF worsening or death. Also, improvements in some measures of dyspnea and health-related quality of life were observed. OBJECTIVES: To demonstrate that bosentan delays IPF worsening or death... CONCLUSIONS: The primary objective in the Bosentan Use in Interstitial Lung Disease-3 trial was not met. Bosentan was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT 00391443).

Rationale and design of a trial on the role of bosentan in Fontan patients: improvement of exercise capacity? [2011.07]
BACKGROUND: The Fontan circulation is a palliative procedure performed in patients with complex congenital heart disease (CHD), making transpulmonary blood flow dependent on the systemic venous pressure. In a Fontan circulation a low pulmonary vascular resistance (PVR) is crucial, as is epitomized by the observation that a high PVR is a strong predictor of mortality. Long-term follow-up has shown that PVR may rise many years after the Fontan procedure has been performed, possibly due to micro-emboli from a dilated right atrium or from the venous system. Other mechanisms of increased PVR might be aging, obstructed airways caused by lymphatic dysfunction, lack of pulsatile pulmonary flow causing a release of endothelium-derived vasoactive molecules, and prolonged overexpression of vasoconstrictors such as endothelin-1. Mean plasma level of endothelin-1 has been shown to be significantly higher in Fontan patients compared to healthy controls. In patients with pulmonary arterial hypertension (PAH), therapy with bosentan, an endothelin-1 receptor antagonist, has demonstrated to improve exercise capacity and to reduce the elevated PVR. In addition, reduction of PVR is shown early and late after the Fontan procedure on treatment with exogenous NO, another advanced PAH therapy. However, the long term effect of reducing the PVR by bosentan treatment on exercise capacity in Fontan patients is still unknown... CONCLUSION: We hypothesize that treatment with bosentan, an endothelin-1 receptor antagonist, improves maximum exercise capacity and functional capacity in adult Fontan patients. Copyright (c) 2011 Elsevier Inc. All rights reserved.

Tadalafil monotherapy and as add-on to background bosentan in patients with pulmonary arterial hypertension. [2011.06]
BACKGROUND: Tadalafil 40 mg orally once daily, was shown to be well-tolerated and efficacious for pulmonary arterial hypertension in a 16-week, double-blind, placebo (PBO)-controlled trial. Inclusion criteria included the option for background bosentan. Analyses of tadalafil in treatment-naive patients and as add-on to bosentan were pre-specified. Objectives were to provide safety and efficacy data for both groups... CONCLUSION: Tadalafil 40 mg was well-tolerated and provided clinical benefit in patients as monotherapy. It was also well-tolerated when added to background bosentan, but data are insufficient to conclude additional benefit. Copyright (c) 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Bosentan treatment of digital ulcers related to systemic sclerosis: results from the RAPIDS-2 randomised, double-blind, placebo-controlled trial. [2011.01]
OBJECTIVES: Ischaemic digital ulcers (DUs) are common in patients with systemic sclerosis (SSc) and are a cause of disease-related morbidity. In an earlier trial, treatment with bosentan, an oral endothelin receptor antagonist, reduced the occurrence of new DUs by 48%. The present study (RAPIDS-2, for 'RAndomized, double-blind, Placebo-controlled study with bosentan on healing and prevention of Ischemic Digital ulcers in patients with systemic Sclerosis') was conducted to more fully evaluate the effects of bosentan treatment on DUs associated with SSc... CONCLUSIONS: Bosentan treatment reduced the occurrence of new DUs in patients with SSc but had no effect on DU healing. Bosentan was well tolerated and may be a useful adjunct in the management of patients with SSc with recurrent DUs.

more studies >>

Clinical Trials Related to Tracleer (Bosentan)

Effects of Bosentan (Tracleer) in the Course of Pulmonary Artery Hypertension Induced by Hypoxia [Completed]
Excessive rise in pulmonary artery pressure induced by low oxygen tension (hypoxia) is one of the factors implicated in high-altitude pulmonary oedema. Plasma ET1 increases in subjects exposed to high altitude and is correlated to pulmonary artery pressure. The aim of the study is to investigate whether blockade of ET1 receptors would reduce the acute rise in systolic pulmonary artery pressure induced by hypoxia.

Effect of Bosentan in Scleroderma Renal Crisis [Active, not recruiting]
Systemic sclerosis (SSc) is a connective tissue disease characterized by excessive collagen deposition, autoimmunity and by vascular hyper-reactivity and obliterative microvascular phenomena that involves multiple organs. Scleroderma Renal Crisis (SRC) occurs in 5% of patients and mainly with diffuse cutaneous SSc. The routine use of angiotensin-converting enzyme inhibitors (ACEI) has been reported to dramatically improve outcome, with a fall of the 12-month mortality from 76% to less than 15% in the United-States. Despite prognostic improvement, SRC remains a severe manifestation of SSc and functional outcome and survival remains poor. Bosentan is a specific, orally active, dual endothelin receptor antagonist that has recently been approved for the treatment of primary pulmonary arterial hypertension and for the prevention of ischemic digital ulcers. Bosentan could have therapeutic benefits on others vascular injuries and particularly in SRC.

Pulmonary Artery Remodelling With Bosentan [Completed]
The main purpose of this study is to investigate whether bosentan (Tracleer) affects the wall thickness of the pulmonary arteries in patients with idiopathic pulmonary arterial hypertension (iPAH) and PAH related to systemic sclerosis (PAH-SSc). The second purpose is to investigate if bosentan affects the enlargement of small vessels in the lungs in response to natural chemicals in patients with iPAH and PAH-SSc.

Bosentan Therapy in Children With Functional Single Ventricle [Completed]
Bosentan is a kind of dual endothelin receptor antagonist. The purpose of this study is to investigate if Bosentan therapy can modify the outcome of children with functional single ventricle.

The Effect of Tracleer on Male Fertility [Completed]
The objective of the study is to evaluate the effects of chronic TRACLEER treatment on testicular function via semen analysis in male patients with primary pulmonary arterial hypertension (PAH).

more trials >>

Reports of Suspected Tracleer (Bosentan) Side Effects

Death (1295)Dyspnoea (1043)Pneumonia (429)Pulmonary Arterial Hypertension (398)Fall (321)Fluid Retention (281)Dizziness (265)Oedema Peripheral (259)Cardiac Failure Congestive (249)Syncope (249)more >>

Page last updated: 2015-10-08

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